This Shared Instrumentation Grant (PAR-12-017) requests funds to purchase an IVIS Spectrum CT in vivo imaging system for non-invasive, longitudinal monitoring of disease progression, cell trafficking and gene expression patterns in living animals through bioluminescent and fluorescent two- or three- dimensional imaging co-registered with small animal computed tomography (CT). Importantly the instrument will be housed within the Pre-Clinical Imaging Core inside the Regional Bio containment Laboratory (RBL) at the University of Pittsburgh offering three major benefits: 1) housing within a 27,000 square foot facility, purpose-built to provide laboratory suites and core facilities operating unde Biosafety Level (BSL)-3 and Animal Biosafety Level (ABSL)-3; 2) registration to handle numerous Select Agent viral and bacterial pathogens and toxins; 3) housing for a wide range of animal species in bio containment caging, from mice to non-human primates (NHPs); 4) association with the Center for Vaccine Research (CVR), whose well-funded faculty have research interests and expertise related to the study of these highly pathogenic organisms and utilize the RBL BSL-3/ABSL-3 containment facilities; 5) a highly trained management team and support staff dedicated to the facility who foster collaborations with other institutions. The IVIS Spectrum CT system will be coregistered for use with existing micro PET/CT imaging capabilities in the CVR/RBL Pre-Clinical Imaging Core, overseen by an established management team and operated by trained personnel to maximize access and use for high-priority pathogen research. The combination of increased interest in research on BSL-3/ABSL-3 pathogens with the increasing availability of technologies for expression of bioluminescent/fluorescent reporters from highly pathogenic organisms as well as for monitoring of disease/immune response parameters highlights our need to improve imaging capabilities in containment. Current and anticipated use of the CVR/RBL laboratories includes pathogenesis and challenge studies in mice, rats, rabbits, ferrets and small NHPs, each of which are amenable to imaging in the IVIS Spectrum CT system. Addition of an IVIS Spectrum CT will: 1) satisfy existing research needs; 2) attract additional researchers regionally or even nationally who wish to integrate live animal imaging into their research; and 3) provide an important capability to the RBL emergency response network. Neither bioluminescence/fluorescence in vivo imaging nor micro CT is available within BSL-3/ABSL-3 containment in this region. Moreover, nationally there are only a few such instruments housed in facilities with BSL-3/ABSL-3 containment and Select Agent security. The diversity of pathogens and animal models available in the University of Pittsburgh RBL and the plan to integrate this IVIS Spectrum CT with existing micro PET/CT imaging capabilities provides a truly unique resource.